Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Otospondylomegaepiphyseal Dysplasia (OSMED) [Q78.9]

OMIM numbers: 215150, 120290 (COL11A2)

Dr. rer. nat. Christoph Marschall

Scientific Background

OSMED is an autosomal recessive disease of the connective tissue, accompanied by severe non-progressive sensorineural hearing loss, enlarged epiphyses, disproportionally short extremities and malformations of the spine. The clinical phenotype of the skeleton overlaps with the autosomal dominant Stickler and Marshall syndromes. Regarding a differential diagnosis, OSMED besides displaying disproportionate extremities distinguishes itself from the others by the absence of sings and symptoms affecting the eyes. Facial dysmorphia such as mid-facial hypoplasia with a short, upturned nose and sunken nasal bridge is characteristic as well.

So far, less than 30 independent cases of OSMED have been described; most of them exhibit mutations in COL11A2. However, there are single cases with COL2A1 mutations. The product of the COL11A2 gene is a component of collagen type XI, which is a heterotrimer of α1(XI), α2(XI) and α3(XI). α3(XI) is encoded by COL2A1 and differs from α1(II) only by its stronger post-translational modification. Moreover, there seems to be an interaction between collagen type XI and II, which has an impact on the regulation of the diameter of the collagen fibrils. This also explains the overlapping spectrum of the phenotypical characteristics of OSMED and collagen type II diseases.